Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment

AbstractDeficiency of ADA2 (DADA2) is the first molecularly described monogenic vasculitis syndrome. DADA2 is caused by biallelic hypomorphic mutations in theADA2 gene that encodes the adenosine deaminase 2 (ADA2) protein. Over 60 disease-associated mutations have been identified in all domains of ADA2 affecting the catalytic activity, protein dimerization, and secretion. Vasculopathy ranging from livedo reticularis to polyarteritis nodosa (PAN) and life-threatening ischemic and/or hemorrhagic stroke dominate the clinical features of DADA2. Vasculitis and inflammation can affect many organs, explaining the intestinal, hepatological, and renal manifestations. DADA2 should be primarily considered in patients with early-onset fevers, rashes, and strokes even in the absence of positive family history. Hematological manifestations include most commonly hypogammaglobulinemia, although pure red cell aplasia (PRCA), immune thrombocytopenia, and neutropenia have been increasingly reported. Thus, DADA2 may unify a variety of syndromes previously not thought to be related. The first-line treatment consists of TNF-inhibitors and is effective in controlling inflammation and in preserving vascular integrity. Hematopoietic stem cell transplantation (HSCT) has been successful in a group of patients presenting with hematological manifestations. ADA2 is highly expressed in myeloid cells and plays a role in the differentiation of macrophages; however, its function is still largely undetermined....
Source: Journal of Clinical Immunology - Category: Allergy & Immunology Source Type: research